Summit Therapeutics announces topline results from Phase 3 HARMONi trial

Summit Therapeutics (SMMT) announced topline results from the Phase III clinical trial, HARMONi, the first global Phase III study evaluating ivonescimab, successfully met the progression-free survival primary endpoint and showed a positive trend in the other primary endpoint, overall survival. HARMONi is a multiregional, double-blinded, placebo-controlled, Phase III study sponsored by Summit evaluating ivonescimab plus platinum-doublet chemotherapy compared to placebo plus platinum-doublet chemotherapy in patients with epidermal growth factor receptor-mutated, locally advanced or metastatic non-squamous non-small cell lung cancer who have progressed after treatment with a 3rd generation EGFR tyrosine kinase inhibitor. This is a clinical setting with a patient population where PD-1 monoclonal antibodies have previously been unsuccessful in Phase III global clinical trials in showing either a PFS or OS benefit. Approximately 38% of patients were randomized from western countries (ex-Asia), consistent with other recent multiregional Phase III studies in patients with EGFR-mutated NSCLC. At the prespecified primary data analysis, ivonescimab in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival, with a hazard ratio of 0.52. PFS was measured by blinded independent central radiology review committee compared to placebo in combination with chemotherapy. A clinically meaningful hazard ratio was observed in both Asia and ex-Asia sub-populations. The primary analysis demonstrated the consistency of the magnitude of the PFS benefit between patients randomized in Asia and ex-Asia, as well as the consistency in a single-region study with this multiregional study. Ivonescimab in combination with chemotherapy showed a positive trend in OS in the primary analysis without achieving a statistically significant benefit with a hazard ratio of 0.79. This trend provides further support for its use in 2L+ EGFRm NSCLC, a setting where high unmet need continues to exist with limited approved options in the United States and other western territories. There are no current FDA-approved regimens that have demonstrated a statistically significant overall survival benefit in this patient setting. The median follow-up time for western patients was less than the median overall survival at the time of the analysis, and these patients may continue to be followed for long-term outcomes. Both Asian and North American patients demonstrated a positive trend in overall survival. The results of the primary analysis in this multiregional study were consistent with that of the single-region HARMONi-A study, which demonstrated an overall survival hazard ratio of 0.80 at 52% data maturity in a similar patient population. There were no new safety signals noted in this Phase III study. Grade 3 or higher treatment-emergent adverse events were reported for 56.9% of patients in the ivonescimab + chemotherapy arm vs 50.0% with chemotherapy alone. Fatal TEAEs (excluding disease progression) were reported for 1.8% of patients in the ivonescimab + chemotherapy arm vs. 2.8% in those patients receiving chemotherapy alone. The safety profile of ivonescimab + chemotherapy was acceptable and manageable in the context of the observed clinical benefit.